Sensorion's New Drug: SENS-401

This is an update from todays presentation
http://m.4-traders.com/SENSORION-21...-Data-at-ARO-2018-MidWinter-Meeting-25988660/

 

Hello,

I am trying to inform you about the latest results from Sensorion for their treatment called: "SENS-401" I'm French, and I found an English link, so I'm coming to post it to give you some good news. Sorry if my english is sad, I translate it with internet.

https://www.businesswire.com/news/h...Sensorion-Presents-New-SENS-401-Data-ARO-2018

I wish you lots of good things, and do not hesitate to come and ask me news about French research.

Aurelian.

 

Thank you Aurelian,

Not sure this was clear before:

".... Clinical trial planning is ongoing and Sensorion intends to initiate a phase 2 study with SENS-401 in this indication during the first half of 2018."

So we have a third trial planned in 2018 for hearing loss. I'm very curious how SENS-401 actually repairs the inner ear.

 

Sorry, I had not seen that one the conversation dedicated for Sensorion.
I am curious also. Apparently, it would be compressed(restrained) to set during 28 days, but it seems to me "too easy" to get back the hearing after a month. i have T since 4 years and H since 1 year but I am sure that 2018 will be beneficial for us

#Hope

 

Isn't it only for acute hearing loss? Or are they able to restore hearing after a year?

 

"Early clinical data for SENS-401 have previously provided compelling scientific rationale for further clinical evaluation. Pre-clinically, oral doses of SENS-401 versus placebo were tested in models of severe noise-induced hearing loss and cisplatin induced ototoxicity. In both models, SENS-401 demonstrated significant improvement of hearing and enhancement of outer hair cell survival vs placebo"

So I understand it works for hearing loss as well. It does not sound spectacular but who knows. Unfortunately no reports with results achieved in the lab.

 

Isn't it only for acute hearing loss (sudden sensorineural hearing loss (SSNHL))?

SENS-401, the Company’s drug candidate being developed for the treatment of acute sensorineural hearing loss

A first-in-class drug to treat Sudden SensoriNeural Hearing Loss (SSNHL).

• To protect against inner ear lesions that lead to nerve degeneration and hair cells loss
• Received Orphan Drug Designation in Europe for treating SSNHL

SSNHL is also known as sudden deafness and belongs to the group of rare conditions that affect the inner ear (Rapid (instant or in <72 hours) hearing loss typically unilateral)

 

I think that after re-reading the article it is acute HL. Sorry for the confusion.

 

Sensorion (FR0012596468 – ALSEN) (Paris:ALSEN), a biotech company specializing in the treatment of inner ear diseases, today announces new data presented in multiple poster presentations at the Association for Research in Otolaryngology’s (ARO) 41st Annual MidWinter Meeting in San Diego, California, which took place February 9th to 14th, 2018.

SENS-401 translational research:

• Twice versus once daily oral dosing of SENS-401 for 28 days reveals exposure duration driven treatment effect against severe acoustic trauma induced hearing loss in rats.

This study compared the efficacy of twice daily low dose versus once daily high dose oral administration of SENS-401, and results suggested that the daily duration of drug exposure is more important than maximal dose drug exposure for the otoprotective efficacy of SENS-401. Results also showed that a 28-day treatment provides better hearing outcome than a 14-day treatment. There is currently no approved pharmaceutical treatment for hearing loss. SENS-401 is Sensorion’s clinical-stage small molecule drug candidate with orphan drug designation for treatment of Sudden Sensorineural Hearing Loss (SSNHL) and cisplatin-induced ototoxicity (CIO), and has previously demonstrated an ability to reduce hearing loss and enhance survival of outer hair cells of rats exposed to acoustic trauma or cisplatin infusion.

• Translational development of the clinical stage oral otoprotectant SENS-401 for sensorineural hearing loss.

Early clinical data for SENS-401 have previously provided compelling scientific rationale for further clinical evaluation. Pre-clinically, oral doses of SENS-401 versus placebo were tested in models of severe noise-induced hearing loss and cisplatin induced ototoxicity. In both models, SENS-401 demonstrated significant improvement of hearing and enhancement of outer hair cell survival vs placebo. Additionally, pharmacokinetic profile and dose dependency were evaluated. A phase 1 clinical trial demonstrated that SENS-401 was well tolerated by patients and determined that the clinical pharmacokinetic profile is consistent with the drug exposures needed for preclinical efficacy. Clinical trial planning is ongoing and Sensorion intends to initiate a phase 2 study with SENS-401 in this indication during the first half of 2018.

Tinnitus preclinical research:

• Tinnitus or Hearing Loss? Relationship between GPIAS deficits and ABR thresholds after repeated salicylate administration in rats.

The gap-prepulse inhibition of acoustic startle (GPIAS) paradigm using salicylate induction is widely used in preclinical settings for the study of tinnitus. The GPIAS behavioral paradigm measures the ability of a silent gap in background noise to inhibit the startle response to a loud noise. Salicylate is often used because it rapidly induces deficits in startle inhibition by gap-detection which are interpreted as tinnitus-related. However, recent work emphasizes that hearing loss can be a confounding variable using the GPIAS paradigm, rendering a straightforward interpretation of gap-detection deficits as a clear measure of tinnitus difficult. This study demonstrated that there is a strong relationship between salicylate-induced hearing loss and gap-detection deficits using the GPIAS paradigm. Results from this study emphasize the need for concurrent control measurements of hearing ability when using the GPIAS paradigm to assess tinnitus, particularly in animal models with bilateral hearing impairment.

https://www.businesswire.com/news/h...Sensorion-Presents-New-SENS-401-Data-ARO-2018

 

Sensorion will be presenting some preclinical results at the American Neurotology Spring meetings: http://www.sensorion-pharma.com/images/press_release/20180409-PR-EN-ANS-COSM_Curtain_Raiser-VF.pdf Title of the presentation is "The Clinical Stage Otoprotectant SENS-401 Effectively Reduces Hearing Loss in Rats When Administered up to 96 hours after Severe Acoustic Trauma"

They are also presenting a paper on a blood biomarker for hearing loss.

They have also posted their 2017 corporate results: http://www.sensorion-pharma.com/ima..._Annual-2017-Financials-results-VF11april.pdf

 

Even if it is only for acute hearing loss. Just because we have tinnitus, doesn't mean that we cannot get more acute hearing loss stacked upon our already existing hearing loss.

Just imagine the scenario where you have to take a medication that you know is ototoxic but you have no choice. Or you experience major hearing loss through other reasons.

Wouldn't it be nice to have a medicine that could protect your ear from any further hearing loss and therefore more tinnitus? I for one would be super excited to have that option.

 

In this (https://globenewswire.com/news-rele...ed-Up-to-Four-Days-after-Acoustic-Trauma.html) ridiculously hyped press release we learn a bit of interesting information. (In addition to the hype, its very odd they talk about SSNHL after acoustic trauma. Part of why SSNHL is challenging in that there is no obvious cause.)

Anyway, here is the interesting bit with emphasis added "In the study, beginning from 24 to 96 hours after severe acoustic trauma, rats orally received either 13.2 mg/kg SENS-401 or placebo control twice daily for 28 days. Hearing outcomes and otoprotection were evaluated via auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing as well as cochleograms. SENS-401 treatment significantly improved recovery of hearing loss in rats when initiated up to 96 hours after severe acoustic trauma (p=0.006) as well as enhancing the survival of sensory outer hair cells (p=0.027). "

The improvement in hearing loss is of course a good thing, but preserving outer hair cells is very important for improving thresholds. With p=0.027, it's not hugely statistically significant, but any evidence of this is a good thing.

 

Agreed
Its a classic pump and dump.
Shareholders probably paid for this press release and have their fingers on the trigger, but the market does not seem to be fooled.

 

http://www.sensorion-pharma.com/images/press-release/20181107-PR-Sensorion_Neurocience_2018_EN.pdf

 

http://www.sensorion-pharma.com/images/press-release/20181221-PR-SENS401-OtoNeuroJournal.pdf

The Sensorion pre-clinical team tested the efficacy of SENS-401 against severe acoustic trauma-induced hearing loss in a male rat model using auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE) and histology. Results showed that twice daily, lower doses of SENS-401 for 28 days was the optimal dosing regimen for hearing protection using all outcome measures. Further experiments demonstrated that this treatment regimen was able to deliver clinically relevant and statistically significant otoprotection and hearing recovery when the administration was delayed by as much as 96 hours after acoustic trauma (the latest treatment initiation time-point tested). A responder analysis showed that oral SENS-401 treatment not only strongly increased the percentage of subjects with clinically significant hearing recovery compared to placebo, but also enhanced the degree of individual hearing recovery observed. These data on otoprotection and hearing recovery supports SENS-401 as a promising clinical candidate for acute onset sensorineural hearing loss, including when treatment is not initiated immediately. “These results provide support for the translational development of SENS-401 in sudden sensorineural hearing loss (SSNHL) and publication in the respected Otology & Neurology journal also provides additional important peer-validation,” says Nawal Ouzren, Sensorion’s Chief Executive Officer. “SENS-401 offers the potential to make a real difference to patients’ lives as a potential first-in-class treatment, and we look forward to starting the Phase 2 of SENS-401 in SSNHL for which we received the authorization in Europe and Canada.”

 

Sensorion (ALSEN) (FR0012596468 – ALSEN) a pioneering clinical-stage biopharmaceutical company which specializes in the development of novel therapies to restore, treat and prevent inner ear diseases such as hearing loss, tinnitus and vertigo, today announced that the independent Data Safety Monitoring Board (or DSMB) has undertaken a review of the safety data for the 76 first patients having completed the phase 2 clinical trial for SENS-111 in the treatment of acute unilateral vestibulopathy(AUV).

https://www.marketwatch.com/press-r...cute-unilateral-vestibulopathy-auv-2019-05-15

 

Sensorion Receives FDA IND Approval for Arazasetron (SENS-401)

https://finance.yahoo.com/news/sensorion-receives-fda-ind-approval-053000700.html

 

Sensorion announces €5.6m non-dilutive funding to support SENS-401 Phase 2 study in Sudden Sensorineural Hearing Loss French ministry of armed forces to participate in the study

https://www.sensorion-pharma.com/images/press-release/20191223-PR-SENS401-PATRIOT-PSPC.pdf

Good news I guess even if tinnitus is not measured in secondary outcome of the study and it only includes unilateral hearing loss. Still, things are moving forward and positively. Bear in mind that earlier in December their drug on vestibulopathy (SENS-111) failed to show efficacy in Phase 2 trial. So things weren't looking really great for Sensorion. Looking forward to the Phase 2 trial !

 

Can someone provide some insight into this slide?



Because it seems to imply from additional data on the right that the result in the picture above from SENS-401 was post noise trauma and not preventative.

Which means they were getting reorganization and regeneration of the OHC with this compound and I’m very confused how that is possible.

Am I reading the data wrong, could someone help? https://www.sensorion-pharma.com/im...20200130-Corporate_Presentation_Sensorion.pdf

 

It says it was given up to 96 hours post noise trauma. So it looks like a treatment for permanent damage if given acutely.

 

Just to recall: https://clinicaltrials.gov/ct2/show/NCT03603314
Efficacy of SENS 401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss (AUDIBLE-S)
Actual Study Start Date : February 15, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : August 30, 2022

 

And Pipeline according to their website:

 

Is this a preventative drug or can it restore hair cells as well?

 

Does anyone know the answer to this?

 

It doesn't restore hair cells. You can give it right after an acoustic trauma to "treat" the damage that would otherwise destroy the hair cells:

https://www.sensorion.com/en/fiches-produits/sens-401-2/#SENS-401SSHNL

In that sense it's more of a preventative except by technicality.

 

Oh OK, thanks.

 

Phase 2 failed =(

SENS-401 was safe and well tolerated, however, it did not meet the primary endpoint of 15 dB, a significant improvement in pure tone audiometry (PTA, dB) in the affected ear from baseline in comparison to placebo at the end of the four-week treatment period.

https://www.sensorion.com/en/category/press-releases/

 

Let's hope 4 weeks was long enough for any hair cells that would regenerate to regenerate. Also we don't know; it is entirely possible that the hair cells regenerated but did not connect to the nerves. Might need a dual drug therapy that delivers the hair cell re-generator and then a cochlear synapse terminal re-generator like OTO-413.

 

What, are these guys serious, it is not only about damn dB increase. If clarity or speech perception in noise improved as well, then the drug works. It's much more deeper and complicated than just damn stupid audiogram measurement.

Sometimes I feel those experts in field have to experience by themselves what it means to have hearing loss, or just listen to musicians who have lost their hearing somehow, because as musician I was able to identify it really fast what has happened, what is happening and what was lost at first.

 

They're still evaluating it for secondary endpoints.